Discrimination of lipid composition and cellular localization in human liver tissues by stimulated Raman scattering microscopy

Fiona Xi Xu, George N. Ioannou*, Sum P. Lee, Christopher Savard, Christian L. Horn, Dan Fu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Significance: The molecular mechanisms driving the progression from nonalcoholic fatty liver (NAFL) to fibrosing steatohepatitis (NASH) are insufficiently understood. Techniques enabling the characterization of different lipid species with both chemical and spatial information can provide valuable insights into their contributions to the disease progression. Aim: We extend the utility of stimulated Raman scattering (SRS) microscopy to characterize and quantify lipid species in liver tissue sections from patients with NAFL and NASH. Approach: We applied a dual-band hyperspectral SRS microscopy system for imaging tissue sections in both the C–H stretching and fingerprint regions. The same sections were imaged with polarization microscopy for detecting birefringent liquid crystals in the tissues. Results: Our imaging and analysis pipeline provides accurate classification and quantification of free cholesterol, saturated cholesteryl esters (CEs), unsaturated CE, and triglycerides in liver tissue sections. The subcellular resolution enables investigations of the heterogeneous distribution of saturated CE, which has been under-examined in previous studies. We also discovered that the birefringent crystals, previously found to be associated with NASH development, are predominantly composed of saturated CE. Conclusions: Our method allows for a detailed characterization of lipid composition in human liver tissues and enables further investigation into the potential mechanism of NASH progression.

Original languageEnglish
Article number016008
JournalJournal of Biomedical Optics
Volume29
Issue number1
DOIs
StatePublished - 1 Jan 2024
Externally publishedYes

Keywords

  • fibrosing steatohepatitis
  • human liver tissue
  • lipid
  • nonalcoholic fatty liver disease
  • stimulated Raman scattering microscopy

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